Several amphibian, opioid receptor, peptide agonists were used to (A) generate supporting evidence for the existence of mammalian counter parts in rat brain and (B) show how such compounds may aid in characterization of the p (peripheral pain) receptor. (A) Immunohistochemical analysis performed with relatively high-affinity antisera to dermorphin showed that a demorphin-like material (Dr-LM) is present in cell bodies of the rat medial basal hypothalamus; there may be a relationship between existence of Dr-LM (a structurally-related peptide procursor) and the documented ability of intracerebroventriculary administered dermorphin to elevate serum prolactin levels. Estradiol receptor-containing cell bodies in this brain region contain POMC (preopiomelanocotin); however, Dr-LM is not a component of POMC. Antiserum to DGAP (L-amino acid-containing homolog of deltorphin) cross-reacts with cells in the hyperphysiotrophic region of the median emminence; further study is ongoing. Structural homology between the amino acid sequence of dermorphin (or DGAP) andPOMC, or most other proteins in the GCG database, is very low, thus, suggesting that the propeptide is unknown. (B) Ferrirea and co-workers have proposed that the P opioid receptor system(s) facilitates morphine down-regulation of pain receptors by a nitric oxide-cGMP pathway. Two selective, high affinity opioid receptor peptide agonist, dermorphin (mu agonist) and deltorphin (delta agonist), were found to be effective analgesics when tested by Ferrirea on the P receptor; DGAP (L-Met2 deltorphin) and DAGO (reference agonist) were ineffective at tested dosages. P receptor responsiveness to selective, high affinity antagonists differed from those characteristic of opioid receptors in the central nervous system.